کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1361426 | 981463 | 2008 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Structure-activity study of 2,3-benzodiazepin-4-ones noncompetitive AMPAR antagonists: Identification of the 1-(4-amino-3-methylphenyl)-3,5-dihydro-7,8-ethylenedioxy-4H-2,3-benzodiazepin-4-one as neuroprotective agent
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Structure-activity study of 2,3-benzodiazepin-4-ones noncompetitive AMPAR antagonists: Identification of the 1-(4-amino-3-methylphenyl)-3,5-dihydro-7,8-ethylenedioxy-4H-2,3-benzodiazepin-4-one as neuroprotective agent Structure-activity study of 2,3-benzodiazepin-4-ones noncompetitive AMPAR antagonists: Identification of the 1-(4-amino-3-methylphenyl)-3,5-dihydro-7,8-ethylenedioxy-4H-2,3-benzodiazepin-4-one as neuroprotective agent](/preview/png/1361426.png)
چکیده انگلیسی
In the search for AMPA receptor (AMPAR) antagonists, 2,3-benzodiazepines represent a family of specific noncompetitive antagonists with anticonvulsant and neuroprotective properties. We have previously shown that 2,3-benzodiazepin-4-ones possess marked anticonvulsant properties and high affinity for the noncompetitive binding site of the AMPAR complex. In this paper, we report the synthesis and pharmacological characterization of a full set of 2,3-benzodiazepin-4-ones in order to better define the structure-activity relationship (SAR) of this class of compounds. Binding assays and functional tests were performed to evaluate the antagonistic activity at the AMPARs. Through these results we have identified a potent AMPAR antagonist, 1-(4-amino-3-methylphenyl)-3,5-dihydro-7,8-ethylenedioxy-4H-2,3-benzodiazepin-4-one (5c). This compound noncompetitively inhibited AMPAR-mediated toxicity in primary mouse hippocampal cultures with an IC50 of 1.6 μM and blocked kainate-induced calcium influx in rat cerebellar granule cells with an IC50 of 6.4 μM. Thus, 5c has the in vitro potential as therapeutic drug in the treatment of various neurological disorders.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 16, Issue 5, 1 March 2008, Pages 2200-2211
Journal: Bioorganic & Medicinal Chemistry - Volume 16, Issue 5, 1 March 2008, Pages 2200-2211
نویسندگان
Nicola Micale, Simona Colleoni, Giovanna Postorino, Alessia Pellicanò, Maria Zappalà , John Lazzaro, Valentina Diana, Alfredo Cagnotto, Tiziana Mennini, Silvana Grasso,